These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: ClC-2 regulates mucosal barrier function associated with structural changes to the villus and epithelial tight junction.
    Author: Nighot PK, Blikslager AT.
    Journal: Am J Physiol Gastrointest Liver Physiol; 2010 Aug; 299(2):G449-56. PubMed ID: 20489043.
    Abstract:
    We have previously shown an important role of the chloride channel ClC-2 in orchestrating repair of tight junctions in ischemia-injured mucosa. In this study, we examined the role of ClC-2 in regulating barrier function of normal murine intestinal mucosa. Ex vivo, ClC-2-/- ileal mucosa mounted in Ussing chambers had significantly higher transepithelial electrical resistance (TER) and reduced [(3)H]mannitol mucosal-to-serosal flux compared with wild-type (WT) mouse mucosa. We also noted that ileum from ClC-2-/- mice had a significantly reduced in vivo [(3)H]mannitol blood-to-lumen clearance compared with WT animals. By scanning electron microscopy, flat leaflike villi were found to have tapering, rounded apical tips in ClC-2-/- mucosa. By transmission electron microscopy, the apical intercellular tight junctions in ClC-2-/- intestine revealed lateral membranes that were less well defined but closely aligned compared with electron-dense and closely apposed tight junctions in WT mucosa. The width of apical tight junctions was significantly reduced in ClC-2-/- intestine. Such an alteration in tight junction ultrastructure was also noted in the testicular tissue from ClC-2-/- mice. The ClC-2-/- intestinal mucosa had reduced expression of phospho-myosin light chain (MLC), and inhibition of myosin light chain kinase (MLCK) in WT mucosa partially increased TER toward the TER in ClC-2-/- intestine. Contrary to our prior work on the reparative role of ClC-2 in injured mucosa, this study indicates that ClC-2 reduces barrier function in normal mucosa. The mechanisms underlying these differing roles are not entirely clear, although ultrastructural morphology of tight junctions and MLCK appear to be important to the function of ClC-2 in normal mucosa.
    [Abstract] [Full Text] [Related] [New Search]